Bariatric Surgery Is Associated with Alcohol-Related Liver Disease and Psychiatric Disorders Associated with AUD.

BACKGROUND/AIMS: Bariatric surgery can increase the risk of addictive disorders and nutritional deficiencies. The aim of this study was to evaluate the association between bariatric surgery and alcohol use disorder (AUD), alcohol-related liver disease (ALD), and psychiatric disorders associated with AUD. The impact of vitamin D deficiency in these associations was also investigated. METHODS: A cross-sectional study was performed using the National Inpatient Sample database and its ICD-9 codes information. Diagnostic and comorbidity data from hospital discharges were obtained from patients with bariatric surgery and other abdominal surgeries between 2005 and 2015. The two groups were then compared for alcohol-related outcomes after propensity-score matching. RESULTS: The final study cohort included 537,757 patients with bariatric surgery and 537,757 with other abdominal surgeries. The bariatric surgery group had an increased risk of AUD [odds ratio (OR): 1.90; 95% CI: 1.85-1.95], ALD [OR: 1.29; 95% CI: 1.22-1.37], cirrhosis [OR, 1.39; 95% CI: 1.37-1.42], and psychiatric disorders associated with AUD [OR, 3.59; 95% CI: 3.37-3.84]. Vitamin D deficiency did not impact in the association between bariatric surgery and AUD, ALD, or psychiatric disorders associated with AUD. CONCLUSIONS: Bariatric surgery is associated with an increased prevalence of AUD, ALD, and psychiatric disorders associated with AUD. These associations appear to be independent from vitamin D deficiency.

Poor Outcomes of Patients With NAFLD and Moderate Renal Dysfunction or Short-Term Dialysis Receiving a Liver Transplant Alone.

The outcomes of patients with moderate renal impairment and the impact of liver disease etiology on renal function recovery after liver transplant alone (LTA) are largely unknown. We explored whether NAFLD patients with pre-LTA moderate renal dysfunction (GFR 25-45 ml/min/1.73 m2) may be more susceptible to develop post-LTA severe renal dysfunction (GFR<15 ml/min/1.73 m2) than ALD patients, as well as other overall outcomes. Using the UNOS/OPTN database, we selected patients undergoing liver transplant for NAFLD or ALD (2006-2016), 15,103 of whom received LTA. NAFLD patients with moderate renal dysfunction were more likely to develop subsequent GFR<15 ml/min/1.73 m2 than ALD patients (11.1% vs. 7.38%, p < 0.001). Patients on short-term dialysis pre-LTA (≤12 weeks) were more likely to develop severe renal dysfunction (31.7% vs. 18.1%), especially in NAFLD patients, and were more likely to receive a further kidney transplant (15.3% vs. 3.7%) and had lower survival (48.6% vs. 50.4%) after LTA (p < 0.001 for all). NAFLD was an independent risk factor for post-LTA severe renal dysfunction (HR = 1.2, p = 0.02). NAFLD patients with moderate renal dysfunction and those receiving short-term dialysis prior to LTA are at a higher risk of developing subsequent severe renal dysfunction. Underlying etiology of liver disease may play a role in predicting development and progression of renal failure in patients receiving LTA.

Non-malignant portal vein thrombosis in a cohort of cirrhotic patients: Incidence and risk factors.

AIM: Non-malignant portal vein thrombosis (PVT) is a complication of liver cirrhosis. The aim of this study was to evaluate the annual incidence of PVT and related risk factors. METHODS: We retrospectively reviewed clinical, laboratory, and radiological data collected prospectively from September 2016 to September 2017. A follow-up of 36 months was performed in a subset of patients to determine the cumulative incidence of PVT and related complications. RESULTS: The study included 567 patients. The incidence of PVT at 12, 24, and 36 months was 3.7%, 0.8%, and 1.4%, respectively. Patients with PVT were compared with patients without PVT, and showed differences in albumin (p = 0.04), aspartate aminotransferase (p = 0.04), hemoglobin (p = 0.01), and prothrombin activity (p = 0.01). The presence of hydropic decompensation (57.1% vs. 30.1%; p 0.004), gastroesophageal varices (76.2% vs. 39.5%; p = 0.05), variceal bleeding (52.4% vs. 22.7%; p < 0.001), hepatic encephalopathy (38.1% vs. 9.9%; p = 0.01), spontaneous bacterial peritonitis (9.5% vs. 1.7%; p < 0.001), and use of beta-blockers (71.4% vs. 27.7%; p < 0.001) were significantly associated. In the multivariate analysis, use of beta-blockers and hepatic encephalopathy appeared as risk factors, and high albumin levels a protective factor. CONCLUSIONS: The incidence of PVT was 3.7%. Beta-blockers and hepatic encephalopathy were risks factors. High albumin levels were a protective factor.

Massive impact of coronavirus disease 2019 pandemic on gastroenterology and hepatology departments and doctors in Spain.

BACKGROUND AND AIM: Significant human and material resources have been diverted to coronavirus disease 2019 (COVID-19). Healthcare workers are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We assess the impact of the COVID-19 pandemic on gastroenterology and hepatology departments and specialists in Spain. METHODS: This study involves a nationwide survey addressing the impact of COVID-19 on resources, procedures, and physicians of gastroenterology and hepatology departments in 81 hospitals representative of the Spanish National Health Service. RESULTS: Overall, 41.8% of hospital beds and 40.7% of gastroenterology and hepatology beds were allocated to COVID-19 patient care, as well as 24.8% of gastroenterologists and 58.3% of residents. Outpatient visits, abdominal ultrasounds, and endoscopies were reduced by 81.8-91.9%. Nine large university hospitals had 75% and 89% reductions in therapeutic endoscopies and hepatocellular carcinoma surgery, respectively, with cancelation of elective liver transplant and transjugular intrahepatic portosystemic shunt. Prevalence of infected physicians was 10.6% and was dependent on regional population incidence (r = 0.74, P = 0.001), with 11% hospitalized and one physician dying. Up to 63.4% of physicians may have been infected before or shortly after Spain entered lockdown, 57% of them having recently performed endoscopies. Adequate protection was acknowledged in > 80% hospitals, but only 2.9% performed regular SARS-CoV-2 testing. CONCLUSIONS: The impact of the COVID-19 pandemic on healthcare delivery has been massive. A wave of gastroenterology-related complications is expected because of resource diversion. Gastroenterologists have a high prevalence of infection, although they may have been infected during a first phase of lower awareness and protection. Regular SARS-CoV-2 screening, adequate protection, and quick reorganization of healthcare resources are still needed.

COVID-19 and the digestive system: protection and management during the SARS-CoV-2 pandemic.

The purpose of this rapid review is to provide an update on the impact of SARS-CoV-2 infection on Gastroenterology and Hepatology departments, our patients, and our new way of working. The gastrointestinal tract and the liver are affected by SARS-CoV-2, especially in patients with immunosuppressive therapies. Patients with liver transplantation should be followed closely. Digestive endoscopy is a high-risk procedure for the transmission of SARS-CoV-2. While the pandemic lasts, we must adapt its indications and promote protective measures for patients and healthcare professionals alike. The COVID-19 pandemic has changed our priorities and the way we work, although we do not know what the repercussions will be after normality is reinstated.

Impact of sustained viral response in the evolution of minimal hepatic encephalopathy: A prospective pilot study.

INTRODUCTION AND AIMS: To determine the prevalence of minimal hepatic encephalopathy(MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. MATERIALS AND METHODS: We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. RESULTS: 64 patients were included. 51.6% were male, the median age was 62 years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8kPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24 weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p<0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p=0.02), higher Child-Pugh scores at 24-weeks post-treatment (p=0.04), higher baseline INR levels (1.4 vs. 1.1; p<0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p=0.02). During follow-up, those patients without MHE at 24 weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p=0.04). CONCLUSION: We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.

Permissiveness of human hepatocellular carcinoma cell lines for hepatitis C virus entry and replication.

Hepatitis C virus (HCV) is a globally prevalent pathogen and is associated with high death rates and morbidity. Since its discovery in 1989, HCV research has been impeded by the lack of a robust infectious cell culture system and thus in vitro studies on diverse genetic backgrounds are hampered because of the limited number of hepatoma cell lines which are able to support different aspects of the HCV life cycle. In the current study, we sought to expand the limited number of permissive cells capable of supporting the diverse phases of the HCV life cycle. Initially, we screened a panel of new hepatoma-derived cell lines, designated BCLC-1, -2, -3, -4, -5, -6, -9 and -10 cells, for their ability to express essential HCV receptors and subsequently to support HCV entry by using the well-characterized HCV pseudoparticle system (HCVpp). Apart from BCLC-9, all BCLC cell lines were permissive for HCVpp infection. Next, BCLC cells were subjected to short- and long-term HCV RNA replication studies using HCV subgenomic replicons. Interestingly, only BCLC-1, -5 and -9 cells, supported short-term HCV RNA replication, but the latter were excluded from further studies since they were refractory for HCV entry. BCLC-1, -5 were able to support long-term HCV replication too; yet BCLC-5 cells supported the highest long-term HCV RNA replication levels. Furthermore, cured BCLC-5 clones from HCV subgenomic replicon, showed increased permissiveness for HCV RNA replication. Strikingly, we were unable to detect endogenous BCLC-5 miR122 expression - an important HCV host factor- and as expected, the exogenous expression of miR122 in BCLC-5 cells increased their permissiveness for HCV RNA replication. However, this cell line was unable to produce HCV infectious particles despite ectopic expression of apolipoprotein E, which in other hepatoma cell lines has been shown to be sufficient to enable the HCV secretion process, suggesting a lack of other host cellular factor(s) and/or the presence of inhibitory factor(s). In conclusion, the establishment of these new permissive cell lines for HCV entry and replication, which possess a different genetic background compared to the well-established models, expands the current repertoire of hepatoma cell lines susceptible to the study of the HCV life cycle and also will aid to further elucidate the cellular determinants that modulate HCV replication, assembly and egress.

Validation of noninvasive methods to predict the presence of gastroesophageal varices in a cohort of patients with compensated advanced chronic liver disease.

BACKGROUND AND AIM: The aim was to validate noninvasive methods to predict the presence of gastroesophageal varices (GEV) in patients with suspected compensated advanced chronic liver disease. METHODS: We retrospectively reviewed clinical and radiological data collected prospectively between September 2013 and September 2015. We reviewed 442 consecutive patients with suspected compensated advanced chronic liver disease measured by transient elastography (TE) and a gastroscopy. We evaluated platelets, spleen diameter, TE, liver stiffness × spleen size/platelets (LSPS), variceal risk index (VRI), Baveno VI strategy, and Augustin algorithm. RESULTS: One hundred sixty-one out of 442 patients were included. Patients with GEV were compared with patients without GEV and showed statistically significant differences in platelet count (117 SD 51 vs 149 SD 62; P = 0.02), spleen diameter (13.0 SD 1.9 vs 11.5 SD 2; P = 0.003), and TE (28 SD 15 vs 19 SD 10; P = 0.001). Single methods (platelet count and TE) diagnosed correctly 51% and 71.4% of patients. Combined methods (LSPS, VRI, Baveno VI, and Augustin algorithm) diagnosed correctly 78%, 83.6%, 45.3%, and 57.1% of patients. Patients with GEV misdiagnosed: platelets 5/161 (3.1%), TE 6/161 (3.7%), LSPS 16/159 (10%), VRI 18/159 (11.3%), Baveno VI 3/161 (1.8%), and Augustin algorithm 6/161 (3.7%). Rate of unnecessary gastroscopies: platelets 46%, TE 25%, LSPS 13%, VRI 6%, Baveno VI 53%, and Augustin algorithm 39.1%. CONCLUSIONS: A significant number of patients were classified correctly using TE, LSPS, and VRI; however, LSPS and VRI had unacceptable rates of misdiagnoses. TE is the best noninvasive single method and the Baveno VI strategy the best combined method.

Successful Continuation of HCV Treatment After Liver Transplantation.

BACKGROUND: Guidelines recommend that patients with hepatitis C virus (HCV)-related liver disease be treated for HCV before liver transplant (LT) to eliminate the virus before surgery. However, the unpredictability of donor organ availability may limit treatment duration. Interruption of HCV treatment with resumption post-LT is 1 potential solution which has not been investigated widely. METHODS: Patients from 5 clinical centers included in the large, national, noninterventional Hepa-C registry who started treatment with direct-acting antiviral agents while awaiting LT were identified retrospectively and followed up prospectively. Fifteen patients who had treatment interruptions around LT were identified. RESULTS: The majority of patients (12/15) received interferon-free regimens, most commonly sofosbuvir + daclatasvir (8/12), for a total of 24 weeks (13/15). Treatment was discontinued temporarily for a median of 5 (range, 2-33) days. Fourteen patients completing 12 weeks of follow-up achieved a sustained virological response. One patient who died before week 12 posttreatment achieved a response at posttreatment week 4. Treatment was generally well tolerated. Serious adverse events were recorded in 2 of 15 patients (anaemia in 1 patient; pneumonia in 1 patient); all arose after LT. CONCLUSIONS: Resumption of direct-acting antiviral agent therapy after a temporary interruption around LT was highly effective, achieving sustained virological response in all patients who completed 12 weeks of posttreatment follow-up. Treatment was generally well tolerated pretransplantation and posttransplantation, with a low rate of serious adverse events. Such a strategy may offer an important new approach to the treatment of patients awaiting LT which may be assessed in future studies.

Hepatitis C virus infection inhibits P-body granule formation in human livers.

BACKGROUND & AIMS: Decoding the myriad of interactions that hepatitis C virus (HCV) establishes with infected cells is mandatory to obtain a complete understanding of HCV biology and its associated pathogenesis. We and others have previously found that HCV infection disrupts the formation of P-bodies in cell culture. These are cytoplasmic RNA granules with key roles in post-transcriptional regulation of gene expression. Therefore, P-body disruption might have consequences beyond viral propagation. However, whether P-body disruption occurs also in vivo is unknown. Aim of this study was to address this important issue. METHODS: Formalin-fixed paraffin-embedded liver biopsies from four groups of patients (healthy donors, patients with non-virus related liver inflammation, HCV- and HBV-infected patients) were immunostained to detect DDX6 and Dcp1, two core P-body components. Changes in the localization of these proteins were assessed by confocal microscopy. RESULTS: HCV specifically inhibited P-body formation in hepatocytes from human livers regardless of viral genotype, inflammation grade or whether the infection was recent or long established. Importantly, this alteration was reversed once HCV was eliminated by therapy. Furthermore, we observed in vivo an unexpected heterogeneity in P-body composition, which might reflect functional specializations. CONCLUSIONS: This is the first comprehensive in vivo P-body analysis that links a pathogenic condition to P-body alterations. Because of their role in gene expression, the alteration of P-bodies should be further studied to understand fully complex HCV-associated pathologies.

Imaging of hepatitis C virus infection in liver grafts after liver transplantation.

BACKGROUND & AIMS: The detection of native hepatitis C virus (HCV) antigens in liver tissue may be relevant to diagnostic purposes and to better understand the pathogenesis of HCV infection. The aim of our study was to characterize HCV antigens in liver grafts. METHODS: We selected 32 liver transplant (LT) recipients with recurrent hepatitis C. HCV core and NS5A antigens were detected in formalin-fixed, paraffin-embedded (FFPE) liver biopsies obtained immediately after graft reperfusion (negative controls), during the acute phase of HCV infection (1-6 months) and during follow-up (7-74 months) after LT. Viral antigens were assessed by immunohistochemistry and confocal microscopy. RESULTS: All reperfusion biopsies were negative for both antigens. Core protein was detected in 75% and 33% of acute phase and follow-up biopsies, respectively. HCV antigens were not detected in any of the 10 samples from patients who cleared HCV after antiviral treatment. Immunostaining was hepatocellular, with a granular cytoplasmic pattern and a wide spectrum of intensity. We found a significant association between viral load and the presence of HCV core-positive hepatocytes (p=0.004). NS5A colocalized strongly with core (66%) and adipophilin (36%), supporting the localization of core and NS5A around lipid droplets. A detailed three-dimensional analysis showed that NS5A surrounded the core and adipophilin-positive areas. CONCLUSIONS: HCV antigens can be detected in FFPE liver biopsies by immunohistochemistry. The in vivo colocalization of core and NS5A proteins around the lipid droplets supports that the latter may play a role in virus particle production, similar to what reported in vitro.